The purpose of this study is to test whether surgical insertion of total knee replacement provides further improvement in quality of life, pain and function in addition to an algorithm for systematic non-surgical treatment consisting of corrective insoles, neuromuscular training, weight loss, patient education and pharmacological treatment with paracetamol, NSAIDs and Pantoprazol in patients with knee OA, collectively called the MEDIC-treatment(Medicine Exercise Diet Insoles Cognitive).

The H1-hypothesis is that surgery with insertion of TKR in addition to the MEDIC-treatment results in a greater increase in quality of life and functional capacity and greater reduction in pain than the MEDIC- treatment alone at the primary endpoint, which is follow-up 12months after the start of the treatment.

See statistical analysis plan available under "Links" for further description of the study.

The average score for four of the five KOOS subscales, covering pain, symptoms, difficulties in functions of daily living, and quality of life (KOOS4), with scores ranging from 0 (worst) to 100 (best). Between group comparisons of treatment effect (change in KOOS4 from baseline to 1 year follow-up) will be dependent on data distribution. Between group comparisons of treatment effect (change in KOOS4 from baseline to 1 year follow-up) will be dependent on data distribution. We expect the change to be normally distributed and analysis will be made using a mixed model ANOVA with subject being a random factor and visit (baseline, 3, 6 and 12 months), treatment arm (TKA + MEDIC, MEDIC) and site (Frederikshavn, Farsoe) being fixed factors. Baseline KOOS4 will be a covariate. Furthermore interactions between the fixed factors will be included in the model. P-values and 95% CI will be presented to assess superiority.

Between groups comparisons of the change from baseline to the 1 year follow-up in all secondary endpoint will be handled similar to the primary endpoint. See Statistical analysis plan for further description ("Links")

Adverse events (AE) and seriously adverse events (SAE) will be registered in three ways and divided into index knee or sites other than index knee. The project physiotherapist will record any adverse events that the participant experiences or tells them about. For the participants allocated to, or crossing over to, TKA, a project worker will look through hospital records to register if any pre-defined perioperative and postoperative adverse events occurred. At all follow-ups, the assessor will use open-probe questioning to assess adverse events in all participants

60min. of neuromuscular training two times a week for 3 months (12 weeks) using the neuromuscular training program called NEMEX-TJR.

Other Name: no other names

Drug: Paracetamol

1 g x 4/day

Other Name: no other names

Drug: Burana

400 mg x 3/day for three weeks

Other Name: NSAIDs are chosen in collaboration with the participant.

Drug: Pantoprazol

20mg x 1/day for three weeks

Other Name: no other names

Behavioral: Dietary counseling

For participants with a BMI equal to or >25. The dietitian initiates a 3-month intervention that provides instruction and guidance in relation to diet and plans the number of visits according to the individual participant needs.

Other Name: no other names

Behavioral: Patient education

The aim is to strengthen the participant's involvement in the treatment, so the participant will be in a position to handle, master and act reasonable in relation to their knee OA. This aspect of the intervention is based on principles from The Chronic Disease Self-Management Program, "Lær at leve med kronisk sygdom (Learn to live with chronic illness)" by The National Board of Health, Denmark and "Artrosskolan Spenshult" in Sweden.

Other Name: no other names

Other: Insoles

The position of the knee is assessed using Single Leg Mini Squat. On the basis of this test it is decided which of two types of insoles (Formthotics System) the participant should have (neutral with a lateral wedge or neutral).

The participants will be advised to use the insoles in all shoes.

Other Name: no other names

Active Comparator: MEDIC + TKR

Medicine, Exercise, Diet, Insole and Cognitive/patient education (MEDIC) for three months after a total knee replacement.

Other: Neuromuscular training (NEMEX-TJR)

60min. of neuromuscular training two times a week for 3 months (12 weeks) using the neuromuscular training program called NEMEX-TJR.

Other Name: no other names

Drug: Paracetamol

1 g x 4/day

Other Name: no other names

Drug: Burana

400 mg x 3/day for three weeks

Other Name: NSAIDs are chosen in collaboration with the participant.

Drug: Pantoprazol

20mg x 1/day for three weeks

Other Name: no other names

Behavioral: Dietary counseling

For participants with a BMI equal to or >25. The dietitian initiates a 3-month intervention that provides instruction and guidance in relation to diet and plans the number of visits according to the individual participant needs.

Other Name: no other names

Behavioral: Patient education

The aim is to strengthen the participant's involvement in the treatment, so the participant will be in a position to handle, master and act reasonable in relation to their knee OA. This aspect of the intervention is based on principles from The Chronic Disease Self-Management Program, "Lær at leve med kronisk sygdom (Learn to live with chronic illness)" by The National Board of Health, Denmark and "Artrosskolan Spenshult" in Sweden.

Other Name: no other names

Procedure: TKR

Surgical treatment with insertion of total knee replacement following standard procedures.

Other Names:

Total Knee Replacement

Knee arthroplasty

Other: Insoles

The position of the knee is assessed using Single Leg Mini Squat. On the basis of this test it is decided which of two types of insoles (Formthotics System) the participant should have (neutral with a lateral wedge or neutral).

The participants will be advised to use the insoles in all shoes.

Other Name: no other names

Active Comparator: Observational Cohort

If the patient can be included, but doesn't want to participate in the randomization, the patient is offered to enter into a prospective observational cohort with the same endpoints and the same follow-up as in the randomized study. The participant can then, in consultation with his/her physician, choose whether they would like MEDIC-treatment or TKR in combination with MEDIC-treatment.

Other: Neuromuscular training (NEMEX-TJR)

60min. of neuromuscular training two times a week for 3 months (12 weeks) using the neuromuscular training program called NEMEX-TJR.

Other Name: no other names

Drug: Paracetamol

1 g x 4/day

Other Name: no other names

Drug: Burana

400 mg x 3/day for three weeks

Other Name: NSAIDs are chosen in collaboration with the participant.

Drug: Pantoprazol

20mg x 1/day for three weeks

Other Name: no other names

Behavioral: Dietary counseling

For participants with a BMI equal to or >25. The dietitian initiates a 3-month intervention that provides instruction and guidance in relation to diet and plans the number of visits according to the individual participant needs.

Other Name: no other names

Behavioral: Patient education

The aim is to strengthen the participant's involvement in the treatment, so the participant will be in a position to handle, master and act reasonable in relation to their knee OA. This aspect of the intervention is based on principles from The Chronic Disease Self-Management Program, "Lær at leve med kronisk sygdom (Learn to live with chronic illness)" by The National Board of Health, Denmark and "Artrosskolan Spenshult" in Sweden.

Other Name: no other names

Procedure: TKR

Surgical treatment with insertion of total knee replacement following standard procedures.

Other Names:

Total Knee Replacement

Knee arthroplasty

Other: Insoles

The position of the knee is assessed using Single Leg Mini Squat. On the basis of this test it is decided which of two types of insoles (Formthotics System) the participant should have (neutral with a lateral wedge or neutral).

The participants will be advised to use the insoles in all shoes.

Other Name: no other names

Detailed Description:

Knee osteoarthritis (OA) is the degenerative joint disease that most often requires treatment and at the same time the one associated with the greatest social costs. In addition, the disease has many personal costs and is greatly contributing to reduced functionality and autonomy of older adults.

It is recommended both nationally and internationally that the treatment of knee OA should include multiple treatment modalities. Clinical guidelines recommend that exercise, weight loss and patient education is the first step in treatment and that insoles and pharmacological treatment can be included as a supplement. If this non-surgical treatment is ineffective surgical treatment, especially surgery with insertion of total knee replacement (TKR), may be indicated. There are effects of both non-surgical treatment and TKR, but no studies exist, which examine the effect of surgery with insertion of TKR in addition to the recommended non-surgical treatment of knee OA.

Investigator considers that the mental condition of the participant does not allow participation.

The participant must not be pregnant or plan pregnancy during the study.

Inability to comply with the protocol;.

Inadequacy in written and spoken Danish.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01410409

Locations

Denmark

Department of Occupational and Physiotherapy, Aalborg University Hospital

Aalborg, Denmark, 9000

Farsoe Hospital

Farsø, Denmark, 9640

Vendsyssel Hospital, Frederikshavn

Frederikshavn, Denmark, 9900

Sponsors and Collaborators

Northern Orthopaedic Division, Denmark

The Danish Rheumatism Association

Obel Family Foundation

Spar Nord Foundation

The Bevica Foundation

Aalborg University

Association of Danish Physiotherapists

Formthotics

Medical Specialist Heinrich Kopp's Grant

The Danish Medical Association Research Fund.

Investigators

Principal Investigator:

Søren T Skou, PhD-student

Orthopaedic Research Unit, Aalborg University Hospital, Denmark

Study Chair:

Ewa M Roos, PhD

Institute of Sports Science and Clinical Biomechanics, University of Southern Denmark, Denmark

Study Chair:

Lars Arendt-Nielsen, Dr.Sci.Med.

Center for Sensory-Motor Interaction (SMI), Department of Health Sciences and Technology, Aalborg University